# DEVELOPING T CELLS CLONES CYTOTOXIC TO SARCOMAS

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1989 · $175,484

## Abstract

Trials with non-specifically cytotoxic LAK (lymphokine activated
killer) cells have demonstrated some tumor regression and
substantial toxicity.  The ultimate goal of this proposal is
development of a more effective, safer, specific adoptive
immunotherapy regimen for sarcoma patients through improved
understanding of the immunobiology of the disease and of the
optimal conditions for lymphocyte mediated cytolysis.  The specific
aims of this competing renewal are:

1.  To further explore the nature of the HLA restriction of T cell
clones cytotoxic for sarcomas.  Earlier work indicates a high
prevalence of the HLA-A2 haplotype and a need for concordance at
this haplotype for the generation of specifically cytotoxic
lymphocytes.  HLA-A2 subtypes responsible for target cell
recognition will be defined using isoelectric focusing.  The role
of concordance at other HLA loci in the generation of specifically
cytotoxic T cells will be assessed to determine if the essential
phenomenon is concordance or if there is a specific role for A2.

2.  To continue the comparison of LAK cells and specifically
cytotoxic (educated) T cells.  Presence in culture of HLA-A2+
sarcoma cells precludes development of LAK-like cytotoxicity in
PBLs.  Future studies will assess:  (a) cell surface markers using
monoclonal antibodies, (b) precursors for LAK or specifically
cytotoxic cells using Percoll separation of PBLs, (c) the time in
culture when lymphocytes become committed to LAK or specific
killing and the durability of that commitment, and (d) the role of
HLA concordance in generating LAK or specific killing.

3.  To conduct preclinical therapy trials using human sarcomas
xenografted in nude mice.  Both local (Winn test) and systemic
administration of effector cells will be explored to define:  (a)
relative effectiveness of LAK cells, cloned specifically cytotoxic
T cells, educated PBLs and tumor infiltrating lymphocytes, (b)
optimal dose and schedule of administration of T cells, and (c)
effects of IL-2 alone or with effector cells.

It is hoped that these studies will lead to a better understanding
of the biology of sarcomas and provide reagents for clinical
trials.

## Key facts

- **NIH application ID:** 3178119
- **Project number:** 5R01CA039286-05
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** MICHAEL J MASTRANGELO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $175,484
- **Award type:** 5
- **Project period:** 1984-08-01 → 1991-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178119

## Citation

> US National Institutes of Health, RePORTER application 3178119, DEVELOPING T CELLS CLONES CYTOTOXIC TO SARCOMAS (5R01CA039286-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178119. Licensed CC0.

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